Experience in the Texas Department of Criminal Justice Dermatology Clinic

In this article, the authors review the skin conditions seen in a dermatology referral clinic for inmates in the Texas Department of Criminal Justice system at the University of Texas Medical Branch. A database search of dermatology visits over a 34-month period yielded 3,326 adult outpatient encounters for analysis. Psoriasis, actinic keratoses, and hair diseases were the most commonly encountered diagnoses. Dermatophytes were the most common infection, keloids the most common benign tumor, and pemphigus the most common autoimmune disease.

A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Autoantibodies to BP180 and BP230 can be detected by indirect immunofluorescence (IIF) on different substrates (oesophagus, salt-split-skin, BP180-antigen dots, BP230-transfected cells) and ELISA. Here, we compared test characteristics of these test systems. We analysed sera from BP patients (n=60) in whom the clinical diagnosis had been confirmed histopathologically. The control cohort comprised sera from patients with other autoimmune-associated (n=22) or inflammatory (n=35) skin diseases. All samples were tested by IIF (EUROIMMUN™ Dermatology Mosaic) and ELISA (EUROIMMUN and MBL). Anti-BP180 is best detected with BP180-antigen dots by IIF (sensitivity: 88%; specificity: 97%). As

compared to IIF, the differences with both BP180 ELISA techniques are small though. Likelihood ratios (LRs) for positive and negative test results are >10 and between 0.1 and 0.2, respectively, for all test systems. Detection of anti-BP230 is highly variable (sensitivity range 38-60%; specificity range 83-98%). Only the IIF test reveals a LR for positive test results >10. Since the LRs for a negative test are all ~0.5, negative test results for anti-BP230 antibodies do not help to exclude BP. In conclusion, the multi-parameter IIF test reveals a good diagnostic performance in BP. Since this test simultaneously allows for the detection of anti-Dsg1 and anti-Dsg3 antibodies, involved in pemphigus foliaceus and vulgaris, a single test-incubation may be sufficient to differentiate between the most frequent autoimmune blistering diseases.

Background - Glucocorticoids as sole therapy for pemphigus foliaceus (PF) in cats are not always successful, and it is common to need additional immunomodulating agents to manage the disease. Hypothesis/Objectives - This retrospective study evaluated the use of modified ciclosporin as an adjuvant or sole immunomodulating drug in cats with PF and compared their response to PF cats managed with chlorambucil. Animals - Fifteen client-owned cats diagnosed with PF that received ciclosporin and/or chlorambucil as part of their treatment and had adequate follow-up to assess treatment response were evaluated. Methods - Records were reviewed from feline PF patients presented between the years of 1999 and 2009. Cats were divided into two treatment groups: those treated with ciclosporin and those treated with chlorambucil. Most cats in both groups also received concurrent systemic glucocorticoids. Each group contained six patients. Three cats were treated with both medications and are discussed separately. Time to disease remission, remission-inducing glucocorticoid dose, maintenance or final glucocorticoid dose, disease response and adverse effects were assessed. Results - There was no significant difference in remission times or disease response between groups. All six patients maintained with ciclosporin for PF management were weaned off systemic glucocorticoids, while glucocorticoid therapy was stopped in only one of the six cats receiving chlorambucil. Conclusions and clinical importance - Modified ciclosporin is effective in the management of feline pemphigus foliaceus and is glucocorticoid sparing. PMID: 22731616 [PubMed – as supplied by publisher] (Source: Veterinary Dermatology)http://www.ncbi.nlm.nih.gov/pubmed/22731616?dopt=Abstract

Erythema multiforme (EM) is an uncommon, immune-mediated disorder that presents with cutaneous or mucosal lesions or both. In herpes simplex virus (HSV)–associated EM, the findings are thought to result from cell-mediated immune reaction against viral antigen-positive cells that contain the HSV DNA polymerase gene (pol ). The target lesion, with concentric zones of color change, represents the characteristic cutaneous finding seen in this disorder. Although EM can be induced by various factors, HSV infection continues to be the most common inciting factor. Histopathologic testing and other laboratory investigations may be used to confirm the diagnosis of EM and to differentiate it from other clinical imitators. Imitators of EM include urticaria, Stevens-Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweet’s syndrome, Rowell’s syndrome, polymorphus light eruption, and cutaneous small-vessel vasculitis. Because disease severity and mucosal involvement differ among patients, treatment should be tailored to each patient, with careful consideration of treatment risk vs benefit. Mild cutaneous involvement of EM can be managed primarily with a goal of achieving symptomatic improvement; however, patients with HSV-associated recurrent EM and idiopathic recurrent EM require treatment with antiviral prophylaxis. Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance. With this review, we strive to provide guidance to the practicing dermatologist in the evaluation and treatment of a patient with EM.

Immunoadsorption (IA) has been successfully used in a large variety of autoantibody-mediated disorders. In dermatology, IA is increasingly applied as adjuvant treatment for severe and/or refractory autoimmune bullous diseases. These disorders are characterized by autoantibodies against structural proteins of the skin and/or mucous membranes and include, among others, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid. Autoimmune blistering diseases are associated with a high mortality (pemphigus) or morbidity (bullous pemphigoid) and in particular in pemphigus diseases, treatment is challenging. The pathogenetic role of autoantibodies in most of the immunobullous diseases has been clearly demonstrated, therefore, removal of these autoantibodies is a rational therapeutic approach. IA has been shown to effectively lower the serum autoantibodies and to lead to rapid clinical responses. Most recently, IA has been successfully applied in patients with severe atopic dermatitis and high total serum IgE levels. Here, the different treatment protocols, clinical efficacy, and adverse events are summarized.

The International Pemphigus & Pemphigoid Foundation and Dr. Sarah Brenner recently conducted a survey on some aspects of pemphigus, in particular the gender distribution of the patients, and the relationship between the disease and the use of sex hormones.

This review is different from the usual type of review you might read about bullous diseases in that by being “systematic” it was submitted ahead of time to an independent panel of editors at the Cochrane Collaboration for Evidence-Based Medicine stating that the aim was to summarize data from randomized controlled trials (RCTs) only for the treatment of BP. In addition, how those trials are to be searched for, analyzed and compared is scrutinized.

Out of all the databases only 6 RCTs were published, including 293 patients. One trial compared prednisolone at different doses: 0.75mg/ kg/day vs 1.25mg;/kg/day, and another compared methylprednisolone with prednisolone, and neither study found a significant difference between the two groups, but the patients on the higher prednisolone doses had more severe side effects.

Pemphigus and its variants are rare autoimmune disorders characterized by loss of cell to cell cohesion between keratinocytes leading to intra-epidermal blistering. In all types of pemphigus, antibodies are directed against antigens in the intercellular substance between keratinocytes and in a substantial number of active cases, these pemphigus antibodies can be detected in the general blood circulation.

Pempigus vulgaris (PV) is characterized by flaccid blistering and erosions of the skin and mucous membranes. Involvement within the mouth may often precede the skin erosions and may persist even long after skin lesions subside. It is therefore important to remember that involvement of the oral cavity may take the patient to see dental surgeon, rather than a dermatologist in the first instance. However, in pemphigus foliaceus (PF) the blistering tends to be more superficial than in the vulgaris form of pemphigus and the mucous membrane areas are not involved.

For many years, London, one of the largest cities in the world, has been truly international, with large populations of different ethnic groups living together within a 50 mile radius. This multi ethnicity provides an ideal opportunity to study the epidemiology of pemphigus and provide information on ethnic groups and numbers of involvement. We have recently surveyed our 140 patients of pemphigus who attend our St. John’s Institute for Diseases of the Skin. In our group, the male to female ratio was 1:1.12 (77 F, 63 M) and the mean age of disease onset was 44 years. This of course, is in the prime of adult life and has important economic consequences for patient sufferers, particularly if the disease is severe and the treatment likely to be longstanding. In our patients, the ethnic break-up of our group was British 51 (36.4%), Asian (Indian subcontinent) 46 (32.8%). This is quite a high figure and corroborates other evidence that pemphigus is much more common in patients living in the Indian subcontinent countries. Of Afro-caribbean countries, 15 (10.7%) had pemphigus, Middle-East 12 (8.5%) and curiously, Jewish 9 (6.4%) is rather low, as all the text books state that pemphigus is much more common in those of Jewish ancestry. Others of mixed ethnicity are fewer in number and comprise 2 Greeks and 2 Chinese. This evidence certainly would indicate the genetic factors and have an important role in predisposing individuals to developing pemphigus. It is therefore an opportunity for us to develop this theme further and we will be doing this over the next few years, looking at the genetic haplo types.

For over 25 years, our immunodermatopathological laboratory at our Institute has specialized in diagnosis of auto-immune bullous diseases. We have developed considerable experience with immunofluoresence techniques to detect the presence of antibodies in the skin by the direct method and in the serum by indirect methods. It is now well known that the PF antigen is a transmembrane glycoprotein called desmoglein 1 (Dsg1) and the PV angiten is termed desmoglein 3 (Dsg3). These desmogleins are adhesion molecules belonging to the cadherin family of cell adhesion substances and are very important in keeping the covering of our skin together.

A recent innovation has been the introduction of an antigen specific ELISA test in the diagnosis of pemphigus. The patient’s serum is tested on ELISA plates pre-coated with recombinant proteins of the ectodomain of Dsg1 or Dsg3 antigens (Medical and Biological laboratories Co, Ltd, Nagoya, Japan). Thus specific antibodies directed against Dsg1 or Dsg3 antigens can be detected by this technique.

It was seen that 61% of patients with PV have antibodies to Dsg 1 in addition to Dsg3, and presence of both the antibody types was associated with severe cutaneous and mucosal involvement, while presence of only Dsg3 autoantibodies was associated with pemphigus limited to mucosal surfaces (mainly oral). The proportion of Dsg1 positive PV patients was higher in the Asian ethnic group when compared to their British counterparts. The severity of the skin and oral disease is influenced by the quantities of Dsg1 and Dsg3 antibodies present in a patient.

Conclusion

Whether ELISA plate techniques will eventually overtake immunofluoresence in the diagnosis of pemphigus and related diseases is too early to say, but they are an important advance and enable large numbers of samples to be read quite quickly. I am sure those of you who are interested in pemphigus will see much more on this in the future about diagnostic techniques. Clearly, accurate diagnosis will ultimately lead to the potential of good targeted therapies.

I will attempt to clarify what we know about the antibody response in various forms of pemphigus and how the distribution of the targeted antigens affects the location of lesions. The synthesis of this work has been proposed by Dr. John Stanley, with key published advances from Dr. Masa Amagai and Mai Mahoney, Ph.D., P. Koch and others. John Stanley refers to his concept as the “desmoglein compensation hypothesis”. The key to this hypothesis is the desmogleins (pemphigus antigens) are key adhesion molecules that keep cells attached to each other. In some areas of the body, there are two desmogleins present, and both have to be damaged to cause cell detachment – in some areas only one desmoglein may be present at some level in the skin or mucous membrane, and there only one desmoglein has to be damaged to cause cell detachment.

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of COL17 to test the effect of BP (human) patient-derived
antibodies. Generally, mice are a great experimental
model for studying the human immune system
since the mouse and human systems have been
found to be mechanistically very similar.
The authors genetically removed C3 from the humanized
COL17 mice and showed that indeed, they
lack the complement system. The authors also isolated
four different autoantibodies from four different
BP patients and found they vary in the degree
to which they activate the complement system. All
of the BP antibodies could induce skin detachment
(characteristic of blisters) when injected into either
the normal mice or in the complement-deficient
mice, demonstrating the complement system is likely
not at play in BP blister formation.
They next developed new antibodies that recognize
the exact same portion of COL17 and found a
correlation between the level of COL17 recognized
by the autoantibodies and blister formation. Recent
studies have shown COL17 antibodies not only recognize
and bind COL17 but also deplete it from cultured
cells. Ujiie and colleagues repeated that result show it
is complement-independent. As well, they find the
same effect of COL17 depletion in the COL17-humanized
mice - the antibodies caused blisters and
simultaneously reduced the amount of COL17.
Finally, the authors found that this was due to an
induction of the ubiquitin-proteasome system, the
machinery of cells that acts as a garbage disposal for
unwanted proteins. In this case, the COL17 autoantibodies
somehow mark the otherwise normal COL17
for destruction, possibly setting the stage for BP
symptoms and disease.
Several mechanisms may still be at play to mediate
the effects of COL17 autoantibodies generated
by BP patients (see figure). These include a degradation
system, as suggested from the current work or
COL17 may be internalized into cells upon binding of
the autoantibodies, as has been seen in studies from
other labs. It is also possible that COL17 gets internalized
first and then the intracellular proteasome
system degrades it. In any case, COL17 targeting by
BP autoantibodies is a probably occurring by a more
direct mechanism than if it involved the complement
system.
It is possible that BP shares a mechanistic basis with
other autoimmune mucocutaneous diseases such as
pemphigus vulgaris, where autoantibodies recognize
desmoglein proteins Dsg1 and Dsg3 in keratinocytes
of the epidermis. Therefore, understanding the underlying
mechanisms at play in blister formation in
the various P/P diseases will be applicable to all patients